Using the phytohemagglutinin-stimulated human lymphocyte as a model system, the proposed research is designed to study the role of zinc in cellular differentiation. The objectives of this study are: 1) To answer the question of how zinc gets to the lymphocyte, by studying the interaction of zinc transferrin with lymphocytes. Using radioiodinated zinc transferrin, binding of protein to lymphocytes will be determined by both an in vitro binding assay and by autoradiography. Additionally, the precise cellular distribution of bound zinc transferrin will also be determined by the immunoperoxidase technique. 2) To study the factors influencing zinc uptake by the lymphocyte, with emphasis on both the metabolic needs of the cell and on compounds which affect cellular levels of cyclic 3', 5'-adenosine monophosphate. 3) To study the distribution of zinc taken up by lymphocytes from zinc transferrin. The fate of incorporated zinc (as Zn65) will be compared for lymphocytes exposed to various compounds, such as corticosteroids, cyclic nucleotides, and adrenergic agents. This will be accomplished by using both autoradiography and subcellular fractionation techniques.